Ampicillin/Sulbactam Treatment Modulates NMDA Receptor NR2B Subunit and Attenuates Neuroinflammation and Alcohol Intake in Male High Alcohol Drinking Rats

Biomolecules. 2020 Jul 10;10(7):1030. doi: 10.3390/biom10071030.


Exposure to ethanol commonly manifests neuroinflammation. Beta (β)-lactam antibiotics attenuate ethanol drinking through upregulation of astroglial glutamate transporters, especially glutamate transporter-1 (GLT-1), in the mesocorticolimbic brain regions, including the nucleus accumbens (Acb). However, the effect of β-lactam antibiotics on neuroinflammation in animals chronically exposed to ethanol has not been fully investigated. In this study, we evaluated the effects of ampicillin/sulbactam (AMP/SUL, 100 and 200 mg/kg, i.p.) on ethanol consumption in high alcohol drinking (HAD1) rats. Additionally, we investigated the effects of AMP/SUL on GLT-1 and N-methyl-d-aspartate (NMDA) receptor subtypes (NR2A and NR2B) in the Acb core (AcbCo) and Acb shell (AcbSh). We found that AMP/SUL at both doses attenuated ethanol consumption and restored ethanol-decreased GLT-1 and NR2B expression in the AcbSh and AcbCo, respectively. Moreover, AMP/SUL (200 mg/kg, i.p.) reduced ethanol-increased high mobility group box 1 (HMGB1) and receptor for advanced glycation end-products (RAGE) expression in the AcbSh. Moreover, both doses of AMP/SUL attenuated ethanol-elevated tumor necrosis factor-alpha (TNF-α) in the AcbSh. Our results suggest that AMP/SUL attenuates ethanol drinking and modulates NMDA receptor NR2B subunits and HMGB1-associated pathways.

Keywords: AMP/SUL; GLT-1; NMDA; ethanol; neuroinflammation.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Alcohol Drinking / adverse effects*
  • Alcohol Drinking / metabolism
  • Ampicillin / administration & dosage
  • Ampicillin / pharmacology
  • Animals
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Encephalitis / chemically induced
  • Encephalitis / drug therapy*
  • Encephalitis / metabolism
  • Excitatory Amino Acid Transporter 2 / metabolism
  • Gene Expression Regulation / drug effects
  • HMGB1 Protein / metabolism
  • Male
  • Rats
  • Receptor for Advanced Glycation End Products / metabolism
  • Receptors, N-Methyl-D-Aspartate / metabolism*
  • Sulbactam / administration & dosage
  • Sulbactam / pharmacology


  • Ager protein, rat
  • Excitatory Amino Acid Transporter 2
  • HMGB1 Protein
  • Hbp1 protein, rat
  • NR2B NMDA receptor
  • Receptor for Advanced Glycation End Products
  • Receptors, N-Methyl-D-Aspartate
  • Slc1a2 protein, rat
  • sultamicillin
  • Ampicillin
  • Sulbactam